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Publication : Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members.

First Author  Certo M Year  2006
Journal  Cancer Cell Volume  9
Issue  5 Pages  351-65
PubMed ID  16697956 Mgi Jnum  J:116441
Mgi Id  MGI:3694305 Doi  10.1016/j.ccr.2006.03.027
Citation  Certo M, et al. (2006) Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members. Cancer Cell 9(5):351-65
abstractText  We show that the antiapoptotic proteins BCL-2, BCL-XL, MCL-1, BFL-1, and BCL-w each bear a unique pattern of interaction with a panel of peptides derived from BH3 domains of BH3-only proteins. Cellular dependence on an antiapoptotic protein for survival can be decoded based on the pattern of mitochondrial sensitivity to this peptide panel, a strategy that we call BH3 profiling. Dependence on antiapoptotic proteins correlates with sequestration of activator BH3-only proteins like BID or BIM by antiapoptotic proteins. Sensitivity to the cell-permeable BCL-2 antagonist ABT-737 is also related to priming of BCL-2 by activator BH3-only molecules. Our data allow us to distinguish a cellular state we call 'primed for death,' which can be determined by BH3 profiling and which correlates with dependence on antiapoptotic family members for survival.
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